Hydroxylation process

ABSTRACT

Hydroxylated aromatic compounds such as phenols are prepared by reacting one or more aromatic compounds with hydrogen peroxide in the presence of trifluoroacetic acid and hydrogen fluoride at a temperature of from -70*C to +50*C.

United States Patent [1 1 Suzuki et al.

[451 Aug. 12, 1975 HYDROXYLATION PROCESS [75] Inventors: Takashi Suzuki; Susumu Naito, both of Niigata, Japan [73] Assignee: Mitsubishi Gas Chemical Company,

Ltd., Tokyo. Japan 22 Filed: Jan. 28, 1974 21 1 Appl. No.: 437,242

[30] Foreign Application Priority Data Jan. 31, 1973 Japan 48-11889 [56] 3 References Cited UNITED STATES PATENTS 2,499,515 3/1950 Fren 260/62] G 3,377,386 4/1968 Chafetzm. 260/621 G 3,407,237 7/1968 Vesely 260/624 R 3,453,332 7/1969 Vesely et a]. 260/613 R 3,481,989 12/1969 V6581) Ct a1. 260/619 R Primary ExamiherBernard Helfin Assistant ExaminerNorman Morgenstern Attorney, Agent, or Firm-Annstrong, Nikaido & Wegner [57] ABSTRACT Hydroxylated aromatic compounds such as phenols are prepared by reacting one or more aromatic compounds with hydrogen peroxide in the presence of trifluoroacetic acid and hydrogen fluoride at a temperature of from 70 C to +50C.

5 Claims, No Drawings l-ethyl-4-methylbenzene,

HYDROXYLATION PROCESS This invention relates to a process for introducing one or more hydroxyl groups into the nucleus of an aromatic compound. More particularly, this invention relates to a process for hydroxylating an aromatic compound comprising treating the aromatic compound with hydrogen peroxide in the presence of trifluoroacetic acid and hydrogen fluoride.

Hydroxylated aromatic compounds such as phenols have been prepared by alkali fusion of a sulfonate, acid decomposition of a hydroperoxide, hydrolysis of an aryl halide, and the like. But there are many disadvantages in these processes in that a large amount of alkali or acid is necessary, it is very difficult to prepare higher phenols other than cresol, and the like. Recently various processes have been proposed on hydroxylation of an aromatic compound using hydrogen peroxide. Typical examples of these processes are (l) by means of H O 'BF=, (J. Org. Chem. 27, 24 (1962)), (2) by means of H O HF (Japanese Pat. Publication Sho 45-13092 (13092/l970)) and (3) by means of H -AlCl (J. Org. Chem. 36, 3184 (1971)). But there are many defects in these processes in that, according to the processes 1 and (3) using BF or AlClas cata lyst, since equimolar or more catalyst is required due to the production of water during the hydroxylation, it is very difficult to recover the catalyst used, and according to the process (2), selectivity of the reaction product is poor although the recovery of the catalyst used is very easy, the yield based on hydrogen peroxide is low, sufficient results can hardly be obtained, and the like.

It is an object of this invention to provide a process for hydroxylating an aromatic compound using hydrogen peroxide overcoming many defects of the previously proposed processes. It is another object of this invention to provide a process for introducing one or more hydroxyl groups into the nucleus of an aromatic compound by one step reaction. It is a further object of this invention to provide a process suitable for a commercial scale production of hydroxylated aromatic compounds. Further objects and advantages of this in vention will be apparent to one skilled in the art from the accompanying disclosure and discussion.

In accordance with this invention, hydroxylated aromatic compounds are prepared by reacting one or more aromatic compounds with hydrogen peroxide in the presence of trifluoroacetic acid and hydrogen fluoride. In the present invention, hydrogen peroxide is activated by the catalyst of trifluoroacetic acid and hydrogen fluoride, the hydroxylation of an aromatic compound can be carried out at a low temperature for a short period, and the" selectivity for the hydroxylated compound is very high, so that the desired compound can be obtained in high yield.

Aromatic compounds such as aromatic hydrocarbon and derivatives thereof can widely be used in the pres ent invention. Preferable examples of the aromatic compounds are as follows:

Benzene; alkylbenzenes such as toluene, p-t amyltoluene, o-xylene, p-xylene, m-xylene, mesitylene, cumene, pseudocumene, hemimellitene, durene, isodurcne, prehnitene, pentamethylbenzene, ethylbenzene,

Lethyl-3-methylbenzene, 1-ethyl-2,3- 1-ethyl-2,4-dimethylbenzene,

l-ethyl-Z-methylbenzene,

dimethylbenzene,

l-ethyl-2,5-dimethylbenzene, 1-ethyl-2.6- dimethylbenzene, 1-ethyl-3,4-dimethylbenzene; l-ethyl-3,S-dimcthylbenzene, l-ethyl-2,3,4-

trimethylbenzene, 1-ethyl2,3,5-trimethylbenzene, lethyl-2,3,o-trimethylbenzene, l-ethyl-2,4,6- trimethylbenzene, 1-ethyl-2,4,5-trimethylbenzene, lethyl-3 ,4,5-trimethylbenzene, l-ethyl-3 ,4,6- trimethylbenzene, l-ethyl-2,3,4,5-tetramethylbenzene, l-ethyl-2,3,4,6-tetramethylbenzene, l-ethyl- 2,3 ,5 ,6- tetramethylbenzene, isopropylbenzene, 1-methyl-2-isopropylbenzene, 1methyl-3-isopropylbenzene, 1-methyl-4-isopropylbenzene, l ,2-dimethyl-3-isopropylbenzene, l,3-dimethyl-4-isopropylbenzene, 1,4- dimethyl-3-isopropylbenzene, 1,3-dimethyl-2-isopropylbenzene, 1,2-dimethyl-4-isopropylbenzene, 1,3- dimethyl-5-isopropylbenzene, 1 ,2,3-trimethyl-4-isopropylbenzene, l ,3 ,4-trimethyl-5-isopropylbenzene, 1 ,2,4-trimethyl-3isopropylbenzene, l,2,4-trimethyl-5- isopropylbenzene, 1,3,5-trimethyl-2-isopropylbenzene, 1 ,2,3-trimethyl-5-isopropylbenzene, 1 ,2,3,4- tetramethyl-5-isopropylbenzene, 1 ,2,3,5-tetramethyl- 6-isopropylbenzene, l,2,4,5-tetramethyl-3-isopropylbenzene, t-butylbenzene, l-t-butyl-3-methylbenzene, 1-t-butyl-4-methylbenzene, l-t-butyl-3,4- dimethylbenzene, l-t-butyl-3,5-dimethylbenzene, l-tbutyl-3,4,5-trimethylbenzene, p-t-butyltoluene, di-tbutylbenzene; t-amylbenzene, t-hexylbenzene; phenol; alkylphenols such as o-cresol, m-cresol, p-cresol, 2,3-

dimethylphenol, 2,4-dimethylphenol, '2,5- dimethylphenol, 2,6'dimethylphenol, 3,4- dimethylphenol, 3,5-dimethylphenol,- 2,3,5- trimethylphenol, 2,3,6-trimethylphenol, 2,4,6- trimethylphenol, 2,3,4 trimethylphenol, p-tbutylphenol, p-t-amylphenol, p-t-hexylphenol, o-tbutylphenol, o-t-amylphenol; dihydroxylated phenols such as hydroquinone, catechol, resorcinol; biphenyl and its alkylated derivatives such as 2,2- dimethylbiphenyl; 2,3 -dimethylbiphenyl, 2,4- dimethylbiphenyl, 3,3'-dimethylbiphenyl, 3,4- dimethylbiphenyl, 4,4"-dimethylbiphenyl; 2-

methylbiphenyl, 3-methylbiphenyl, 4-methylbiphenyl; naphthalene; alkylnaphthalenes such as a-methylnaphthalene, B-methylnaphthalene, 2,6-dimethylnaphthalene, 2,7-dimethylnaphthalene, 1,6-dimethylnaphthalene, t-buty1naphthalene, t-amylnaphthalene; naphthol and its alkylated derivatives such as l-t-butyl-2- naphthol, l-t-amyl-Z-naphthol, l-t-hexyl-2-naphthol; anthracene and its alkylated derivatives such as tbutylanthracene, t-amylanthracene, t-hexylanthracene, t-heptylanthracene, t-octylanthracene; anthrol and its alkylated derivatives such as l-t-butyl-Z-anthrol, l-tamyl'2-anthrol, l-t-hexyl-2-anthrol; phenanthrene and its alkylated derivatives such as t-butylphenanthrene, t-amylphenanthene, t-hexylphenanthene, t-heptylphenanthene, t-octylphenanthrene; phenanthrol and its alkylated derivatives such as l-t-butyl-2-phenantrol; alkoxybcnzencs such as methoxybenzene, ethoxybenzene; methylanisole; halogenated benzene derivatives such as chlorotoluene, bromotoluene, chloroethylbenzene; and the like.

In view of the foregoing, it may be seen that aromatic compounds suitable for use in the present invention in clude, generally, aromatic hyrocarbons which may be substituted by lower alkyl, lower alkoxy, halogen and hydroxy.

The aromatic compounds as mentioned above can be used alone or in admixture, or with aliphatic hydrocarbons or halogenated hydrocarbons inert to the hydroxylation.

Hydrogen fluoride, one component of the catalyst, containing water may be used. The concentration of hydrogen fluoride is generally 70% by weight or more, preferably 80% by weight or more.

The concentration of trifluoroacetic acid, which is the other-component of the catalyst, is generally 80% byweight or more, preferably 85% by weight or more.

moles) of anhydrous hydrogen fluoride were placed in a ZOO-ml autoclave equipped with a stirrer and were cooled below 20C with stirring passing a refrigerant through the jacket. A mixture obtained by dissolving 4.2 g of a 90% by weight hydrogen peroxide solution (corresponding to 0.1 1 mole of hydrogen peroxide) in 21.3 g (0.18 mole) of trifluoroacetic acid was added dropwise to the autoclave under an atmospheric pressure. Since the addition of the hydrogen peroxide solu- The concentration of hydrogen Peroxide is generally tion accompanies much generation of heat, the amount 30% y weight or more, Preferably 50% y Weight or of the recycling refrigerant and the addition of the hydrogen peroxide solution were controlled so as to main- The hydroxylation reaction may be carried out at a i the reaction temperature b l -C Th d temperature between +50C and 70C, Preferably wise addition of the hydrogen peroxide solution took tween and 15 10 minutes. After the completion of the addition of the y Pressure that can maintain the catalyst and a hydrogen peroxide solution, stirring was continued for mixture of an aromatic compound and hydrogen P 10 minutes. The contents were taken out of the autoide in a liquid phase may be used. clave into ice water. The organic matter in the reaction In the ease of mohohydl'oxylahoh of an aromatic mixture was extracted with benzene and dried by a coneompound, the aromatic Compound y Preferably be ventional method. According to the gas chromatoused in excess of hydrogen peroxide. Further in order graphig l i x len l wa obtained in 97 mole to increase the yield based on hydrogen Peroxide, yyield based on the used hydrogen peroxide. The xylenol drogen perixode is used in a molar ratio to an aromatic contained 63 l f 14 /1 34 l f 2 6- compound 1.0 or less, preferably 0.9 or less. In the case l l and 3 mole of 3,5-xy1enol. of polyhydroxylation of an aromatic compound, it is preferable to use a relatively large amount of hydrogen EXAMPLE 2 peroxide, preferably 1 .O 2.0 moles per mole of an aromatic compound Under the same reaction conditions as described in Trifluoroacetic acid may be used 1 mole or more, Example 1 except for g g moles) of preferably 15 moles or more per mole of hydrogen 30 hydrous hydrogen fluor1de,t he hydroxylation was carperoxide. Hydrogen fluoride is generally used 5- 50 xylenol w obtamed 95 mole yield m 0165 preferably 10 30 moles per mole of hydrogen based on the used hydrogen peroxide. The xylenol conperoxide. Hydrogen fluroide is generally used 5 20 tamed 71 mole of z4'xylenol and 29 mole of moles permole of trifluoroacetic acid. In order to carry xylenol out the reaction more smoothly, it is preferable to use 1 mole or more of hydrogen fluoride per mole of water EXAMPLE 3 at the complenon the i A similar autoclave as described in Example 1 was Under the reaction conditlons as mentioned above, used cumen 0 0 20 I 32 6 (O 28 1 hydrogen peroxide can react quantitatively for 5 30 f e g e i mo 6) minutes to yield the corresponding hydroxylated aro- 40 g m uoroacetlc g( es) of anhy' rous hydrogen fluor1de were placed 1n the autoclave. g'o fiifd compound from the stamng aromauc com- A mixture of 4.1 g of a 90% by weight hydrogen perox- The hydroxylated compound obtained is subjected to zigzag?l fg fgg g gf gg ga 3; gigzggzgf z distillation, extraction or neutralization to remove the 5 acid was added dropwise to the Contents of the auto catalyst and is Separated and purified by a conventional clave with vigorous stirring for 15 minutes controlling method' g the reaction temperature below =10C. Stirring was The phenols by h procespf F continued for 30 minutes after the completion of the invention are very important intermediates in chemlcal addition of the mixture lsopropylphenol the m Olaf indflstljies and are use?! for Produci? various, F 5 ratio fo o-isomer: p-isomer being 38 62, was obtained ant1ox1dants, dyes agricultural chem cals, antibacterial in 40% yield based on hydrogen peroxide agents, and medicmes such as vitammes.

The following examples will serve further to illustrate the present invention. EXAMPLES 4 9 Using a similar procedure to that described in Exam- EXAMPLE 1 ple 1, hydroxylations of various aromatic compounds m-Xylene (21.2 g, (0.20 mole)) and 51.4 g (2.57 were carried out. The results were as shown in Table l.

'l'ahlc 1 Example No. 4 5 h 7 N Aromatic Mcsitylunu p-X \lunc 'lolucne l-Ithyll.3-Di111cth \'ll. .-1-'l'rimcth\lcompound hen/one iisopropyli-isoprnpyl hcnlunc benzene Rcactetl amount (molcl Aromatic (1.18 (1.2(1 (LII (1.20 (1.17 (11-; compound 11.0,. 11,1: (111 1111 11.11 11,111 11,111 H1 1.1-1 2. 1 35o 35o 3.511 2.511

Table I -Cntinued launnple No. i (i 7 ('F;;('( )1 )H Reaction temperature l"(') Reaction time lmin.) Yield based on H 0, (mole '1' l lsomcr Lfllllpth lliflli. t isomcr. p-isomer (mole '1' l EXAMPLES l0 15 Using a similar procedure to that described in Example l. hydroxylation of various compounds as listed in Table 2 was carried out. After the reaction, the whole amount of the reaction mixture was placed in a distillation apparatus made of anticorrosive material together with 200 ml of benzene and heated. After distillating the catalyst consisting of hydrogen fluoride and trifluoroacetic acid and the water produced during the reaction with benzene, the resulting benzene solution was analyzed by the gas chromatography. The results were as shown in Table 2.

Comparative Example 2 1n the autoclave, 24.0 g (0.20 mole) of cumene and Table 2 Example No. 10 I I l2 13 14 15 Dimcthyl mXylene *1 Aromatic compound Phenol Anisole nnphthol Mcsitylene Benzene Mcsitylene *2 Reactctl amount (molcl Aromatic comptl. 0.21 I (1.23 0,20 0.17 0,20 *I 025 *2 0.25 H 0 (LII o,|2 (1.11 0.25 0.11 (1.20 Hi" 2.54) 2.58 211i! ",(\(1 15H 2.04 (1i.((X)H 0,13 0.13 mi o 14 0.25 11.30 Reaction temp. 25 -10 5 +5 -.10

((l Reaction time 3U Z0 20 20 30 (min. Yield htlh'ckl on 73 (1) (U (is 30 )5 H O (11101: l

Monoh Xylcnol 1H droxy- Product composition late o-isomcr: 37:63 4113M) l)1l1 \tl1'0X Musitol X2 p-isomcr lulu 45 [mole '9 I The following Comparative Examples 1 and 2 show the effect of hydrogen fluoride or trifluoroacetic acid used alone as catalyst.

Comparative Example 1 In an autoclave similar to that used in Example 1, 35.6 g (0.31 mole) of trifluoroacetic acid and 21.2 g 0.20 mole) of m-xylene were placed and stirred vigorously. A mixture of 4.2 g of a 90% by weight hydrogen peroxide solution (corresponding to 0.1 1 mole of hydrogen peroxide) and 14.9 g (0.12 mole) of trifluoro- This result apparently shows the high activity of the catalyst used in the present invention.

What is claimed is:

l. A process for preparing a hydroxylated aromatic compound which comprises reacting at least one aromatic compound selected from the group consisting of unsubstituted aromatic hydrocarbons and aromatic hydrocarbons substituted with lower alkyl, lower alkoxy, halogen and hydroxy with hydrogen peroxide in the presence of trifluoroacetic acid and hydrogen fluoride at a temperature of from C. to +50C.; at least one mole of trifluoroacetic'acid and 5 to 50 moles of hydrogen fluoride being employed per mole of hydrogen peroxide.

2. A process according to claim 1, wherein 1 mole or less of hydrogen peroxide is used per mole of the aromatic compound in the case of monohydroxylation.

3. A process according to claim 1, wherein 1 mole or more of hydrogen peroxide is used per mole of the aromatic compound in the case of polyhydroxylation.

4. A process according to claim 1, wherein the aromatic compound is an alkylbenzene.

5. A process according to claim 1, wherein the aromatic compound is o-, por m-xylene. 

1. A PROCESS FOR PREPARING A HYDROXYLATED AROMATIC COMPOUND WHICH COMPRISES REACTING AT LEAST ONE AROMATIC COMPOUND SELECTED FROM THE GROUP CONSISTING OF UNSUBSTITUTED AROMATIC HYDROCARBONS AND AROMATIC HYDROCARBONS SUBSTITUTED WITH LOWER ALKYL, LOWER ALKOXY, HALOGEN AND HYDROXY WITH HYDROGEN PEROXIDE IN THE PRESENCE OF TRIFLUOROACETIC ACID AND HYDROGEN FLUORIDE AT A TEMPERATURE OF FROM -70*C. TO +50*C., AT LEAST ONE MOLE OF TRIFLUOROACETIC ACID AND 5 TO 50 MOLES OF HYDROGEN FLUORIDE BEING EMPLOYED PER MOLE OF HYDROGEN PEROXIDE.
 2. A process according to claim 1, wherein 1 mole or less of hydrogen peroxide is used per mole of the aromatic compound in the case of monohydroxylation.
 3. A process according to claim 1, wherein 1 mole or more of hydrogen peroxide is used per mole of the aromatic compound in the case of polyhydroxylation.
 4. A process according to claim 1, wherein the aromatic compound is an alkylbenzene.
 5. A process according to claim 1, wherein the aromatic compound is o-, p- or m-xylene. 